Effects of clonidine premedication on the pressor response to α-adrenergic agonists

Abstract

It has been suggested that postjunctional α1-adrenoceptor mediated vasoconstriction is enhanced by clonidine. We have examined in humans if the presser responses to noradrenaline and phenylephrine are enhanced by clonidine premedication. Seventy-seven patients were allocated randomly to either clonidine (n = 38) or control (n = 39) groups. Patients in the clonidine group received approximately 5 μg kg-1 with famotidine 20 mg, while the control group received famotidine 20 mg alone orally, 90 min before induction of general anaesthesia with thiamylal. In all patients the lungs were ventilated mechanically via tracheal tubes and anaesthesia maintained with 1% end-tidal enflurane and 67% nitrous oxide in oxygen. When a stable haemodynamic state was obtained, either noradrenaline 0.5 μg kg-1 (n = 40) or phenylephrine 2 μg kg-1 (n = 37) was administered randomly i.v. as a bolus, while arterial pressure and heart rate were measured non-invasively at 1-min intervals for 10 min. Although noradrenaline caused significantly greater increases in mean arterial pressure (MAP) in the clonidine group (from 2 to 4 min after i.v. injection) compared with the control group, there were no significant differences in the mean maximal increment in MAP or area under the MAP curve between the two groups. However, i.v. phenylephrine produced a significantly greater increase in MAP from 2 to 7 min (P < 0.05), and greater mean maximal increase in MAP from the baseline value (21 (9) vs 14 (7) mm Hg; P < 0.05) in the clonidine than in the control group. In addition, the duration of elevated MAP in the clonidine group was significantly longer than that in the control group (7.6 (2.4) vs 5.1 (2.8) min; P < 0.01). Furthermore, the area under the curve for MAP changes after i.v. phenylephrine in the clonidine group was significantly greater than that in the control group (69.7 (64.3) vs 11.5 (64.0) mm Hg min, P < 0.01). There were no significant differences in arterial pressure or heart rate after the presser agents between the groups. There were no significant differences between groups in the incidence of hypertension, arrhythmia or bradycardia before or after i.v. noradrenaline or phenylephrine. These results indicate that the presser response to phenylephrine, but not to noradrenaline, is augmented in patients with clonidine premedication.